This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. LDL is defined for lipoproteins that fall into the density range of 1.019-1.063. Within this range, the LDL is in fact a very heterogeneous group of lipoproteins. Conventionally, investigators subdivide LDL into subfractions according to either density or particle size. It is believed that the "small, dense LDL" has a higher propensity of becoming oxidized and therefore, more atherogenic. Other than density and particle size, LDL can also be further divided by their electrical charge by running it through fast protein liquid chromatography against a salt gradient. While other investigators divided LDL into two parts, the electropositive LDL(+) and electronegative LDL(-), Dr. Yang, using a modified protocol, has been able to divide into 5 subgroups, with the 5th group, L5, being most electronegative. Biologically, L5 can induce apoptosis and inflammatory reactions in vascular endothelial cells, it also inhibits EC proliferation and angiogenesis. More recently, we also found it to be able to inhibit differentiation of endothelial progenitor cells. L4 has mild effects, but L1, L2, and L3 are completely harmless. More than 95% of LDL is L1. People with high LDL-cholesterol and/or diabetes, and people who smoke have L5. Nonsmoking healthy subjects do not have L5. One question frequently asked is whether L5 is indeed small dense LDL with a new name. Our preliminary data (in collaboration with Dr. Ron Klause of Berkeley) suggests that it is not the case, but we don't know for sure. One of the primary goals of this collaboration (Chen-Yang-Chiu) is to once and for all determine the structural differences between L5 and other subfractions, in particular L1.